Integrated Bioinformatics Analysis Identified ASNS and DDIT3 as the Therapeutic Target in Castrate-Resistant Prostate
Ae Ryang Jung1, Sun Shin2,3, Mee Young Kim1
1Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Abstract:
Many studies have demonstrated the mechanisms of progression to castration-resistant prostate cancer (CRPC) and novel strategies for its treatment. Despite these advances, the molecular mechanisms underlying the progression to CRPC remain unclear, and currently, no effective treatments for CRPC are available. Here, we characterized the key genes involved in CRPC progression to gain insight into potential therapeutic targets. Bicalutamide-resistant prostate cancer cells derived from LNCaP were generated and named Bical R. RNA sequencing was used to identify differentially expressed genes (DEGs) between LNCaP and Bical R. In total, 631 DEGs (302 upregulated genes and 329 downregulated genes) were identified. The Cytohubba plug-in in Cytoscape was used to identify seven hub genes (ASNS, AGT, ATF3, ATF4, DDIT3, EFNA5, and VEGFA) associated with CRPC progression. Among these hub genes, ASNS and DDIT3 were markedly upregulated in CRPC cell lines and CRPC patient samples. The patients with high expression of ASNS and DDIT3 showed worse disease-free survival in patients with The Cancer Genome Atlas (TCGA)-prostate adenocarcinoma (PRAD) datasets. Our study revealed a potential association between ASNS and DDIT3 and the progression to CRPC. These results may contribute to the development of potential therapeutic targets and mechanisms underlying CRPC progression, aiming to improve clinical efficacy in CRPC treatment.
Insights
Researchers identified key genes, ASNS and DDIT3, linked to castration-resistant prostate cancer (CRPC) progression. High expression of these genes correlates with poorer survival, suggesting potential therapeutic targets for CRPC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Castration-resistant prostate cancer (CRPC) remains a significant clinical challenge with unclear progression mechanisms.
- Current treatments for CRPC are limited, highlighting the need for novel therapeutic targets.
Purpose of the Study:
- To identify key genes involved in CRPC progression.
- To gain insights into potential therapeutic targets for CRPC.
Main Methods:
- Generated bicalutamide-resistant prostate cancer cells (Bical R) from LNCaP cells.
- Utilized RNA sequencing to identify differentially expressed genes (DEGs) between LNCaP and Bical R cells.
- Employed Cytoscape with the Cytohubba plug-in to identify hub genes associated with CRPC progression.
Main Results:
- Identified 631 DEGs, including 302 upregulated and 329 downregulated genes.
- Identified seven hub genes: ASNS, AGT, ATF3, ATF4, DDIT3, EFNA5, and VEGFA.
- ASNS and DDIT3 were significantly upregulated in CRPC cell lines and patient samples.
- High expression of ASNS and DDIT3 correlated with worse disease-free survival in prostate adenocarcinoma patients (TCGA-PRAD dataset).
Conclusions:
- ASNS and DDIT3 show a potential association with CRPC progression.
- These genes may serve as potential therapeutic targets for improving CRPC treatment efficacy.
- Further research into ASNS and DDIT3 could elucidate mechanisms underlying CRPC progression.
